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12.06.2018 | Original Article

Clinical and genetic study of Tunisian families with genetic generalized epilepsy: contribution of CACNA1H and MAST4 genes

verfasst von: Zied Landoulsi, Fatma Laatar, Eric Noé, Saloua Mrabet, Mouna Ben Djebara, Guillaume Achaz, Caroline Nava, Stéphanie Baulac, Imen Kacem, Amina Gargouri-Berrechid, Riadh Gouider, Eric Leguern

Erschienen in: Neurogenetics | Ausgabe 3/2018

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Abstract

Genetic generalized epilepsies (GGE) (childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures (GTCS)) are mainly determined by genetic factors. Since few mutations were identified in rare families with autosomal dominant GGE, a polygenic inheritance was suspected in most patients. Recent studies on large American or European cohorts of sporadic cases showed that susceptibility genes were numerous although their variants were rare, making their identification difficult. Here, we reported clinical and genetic characteristics of 30 Tunisian GGE families, including 71 GGE patients. The phenotype was close to that in sporadic cases. Nineteen pedigrees had a homogeneous type of GGE (JME-CAE-CGTS), and 11 combined these epileptic syndromes. Rare non-synonymous variants were selected in probands using a targeted panel of 30 candidate genes and their segregation was determined in families. Molecular studies incriminated different genes, mainly CACNA1H and MAST4. The segregation of at least two variants in different genes in some pedigrees was compatible with the hypothesis of an oligogenic inheritance, which was in accordance with the relatively low frequency of consanguineous probands. Since at least 2 susceptibility genes were likely shared by different populations, genetic factors involved in the majority of Tunisian GGE families remain to be discovered. Their identification should be easier in families with a homogeneous type of GGE, in which an intra-familial genetic homogeneity could be suspected.

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Titel: Clinical and genetic study of Tunisian families with genetic generalized epilepsy: contribution of CACNA1H and MAST4 genes
verfasst von: Zied Landoulsi
Fatma Laatar
Eric Noé
Saloua Mrabet
Mouna Ben Djebara
Guillaume Achaz
Caroline Nava
Stéphanie Baulac
Imen Kacem
Amina Gargouri-Berrechid
Riadh Gouider
Eric Leguern
Publikationsdatum: 12.06.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Neurogenetics / Ausgabe 3/2018
Print ISSN: 1364-6745
Elektronische ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-018-0550-z

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Clinical and genetic study of Tunisian families with genetic generalized epilepsy: contribution of CACNA1H and MAST4 genes

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